Experimental study shows the potential effects of short-chain PFAS on neurodevelopment

A scientific “One Health” study reveals alterations in cognitive behaviour and neuronal maturation

The pervasive presence and persistence of environmental perfluoroalkyl substances (PFAS)  has, in recent years, elicited considerable interest among the scientific community due to the risk of contamination of water and food sources and the negative effects they have on public health. In humans, early-life exposure to long‑chain PFAS during childhood has been linked to impaired cognitive, motor, and language development, as well as to behavioral alterations. These concerns have progressively led to regulatory restrictions and a growing shift toward the use of short-chain PFAS, as safer alternatives.

A study conducted in a murine model – arising from a partnership among researchers at Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), the IRET Foundation and Bologna University – demonstrated that PFAS, transferred from mother to offspring via the placenta during pregnancy, can activate neurotoxic mechanisms in the developing fetus. Specifically, the administration of the short-chain PFAS – PFBA and GenX – initiated prior to mating and continued throughout gestation and lactation – led to significant impairments in learning, memory, spatial orientation, and cognitive flexibility in the exposed animals.

New experimental evidence links short-chain PFAS exposure to alterations in neurodevelopment. A study conducted in a murine model, arising from a partnership among researchers at Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), the IRET Foundation and Bologna University, and published in Frontiers in Toxicology, demonstrated that PFAS, transferred from mother to offspring via the placenta during pregnancy, can activate neurotoxic mechanisms in the developing fetus.

“This is a highly relevant scientific finding which helps us to understand how these substances, which are currently considered safer alternatives, may still interfere with brain development,” comments Marta Vascellari, veterinarian and Head of IZSVe’s Histopathology Laboratory. “This experimental study marks an important contribution to the ‘One Health’ approach, made possible by a partnership of very distinct research sectors, from human medicine to veterinary medicine, from chemistry to cognitive sciences, with the shared goal of assessing the persistence of short‑chain PFAS in exposed subjects and their potential impact on neurodevelopment.”

PFAS enter the human body primarily through the food pathway, via contaminated food or water. During the highly delicate prenatal and neonatal stages, they can reach the developing organism by crossing the placental barrier during pregnancy and through breast milk after birth. Once absorbed, these substances enter the bloodstream and are distributed across different organs.

“Short-chain PFAS are considered less dangerous than long‑chain ones, due to their lower capacity to accumulate in the body,” states Federica Gallocchio, chemical officer at IZSVe’s Contaminant and biomonitoring laboratory. “Despite occasional detection of short-chain PFAS in drinking water and in human biomonitoring studies, information on the risks to human health associated with diet-related contamination remains limited. PFAS are potentially a “systemic” issue, a contamination chain that – starting from groundwater – may extend to crops, livestock and ultimately reach humans. The aim of this study is to provide robust scientific evidence to support risk assessment and the development of effective prevention strategies to safeguard public health.”

In the experimental procedures described in the study, the administration of the short-chain PFAS – PFBA and GenX – initiated prior to mating and continued throughout gestation and lactation – led to significant impairments in learning, memory, spatial orientation, and cognitive flexibility in the exposed animals. Notably, despite the low (PFBA) or absent (GenX) residual accumulation of these substances in the analysed tissues, observations – particularly following PFBA exposure – revealed delayed neuronal maturation, alterations in neurogenesis, and chronic neuroinflammation. These conditions interfere with hippocampal development and cognitive functions.

The results of the study indicate that the lower propensity of short-chain PFAS to bioaccumulate does not imply reduced toxicity compared with traditional PFAS. They also highlight the need to include neurodevelopmental endpoints in future risk assessments and in regulatory decision‑making regarding the use of these compounds.